Ergothioneine is a thiol-containing amino acid isolated from ergot by Tanret in 1909. Its unique redox-properties makes it one of the best natural anti-oxidants. In addition, due to its specific enrichment from the food by many human tissues (e.g., liver, kidney, central nervous system and red blood cells), ergothioneine was proposed to have many beneficial role in human physiology. Currently, ergothioneine is widely used as the key component in anti-ageing products with a market of billions of dollars.
Ergothioneine is produced from two amino acids (histidine and cysteine) through five-enzymatic steps. However there are three major barriers preventing the utilization of the currently known ergothionine biosynthetic pathway for its production through fermentation: (i) the EgtE enzyme cannot be overexpressed; (ii) the activity of EgtB is low; 3) the potential competition between ergothioneine and glutathione for γ-Glu-Cys, which will limit the production yield. Accordingly, currently, ergothioneine is produced using chemical approaches. As such, there remains a need in the art for recombinant biosynthesis of ergothioneine.